Retention of supraspinal delta-like analgesia and loss of morphine tolerance in δ opioid receptor knockout mice Journal Article
| Authors: | Zhu, Y.; King, M. A.; Schuller, A. G. P.; Nitsche, J. F.; Reidl, M.; Elde, R. P.; Unterwald, E.; Pasternak, G. W.; Pintar, J. E. |
| Article Title: | Retention of supraspinal delta-like analgesia and loss of morphine tolerance in δ opioid receptor knockout mice |
| Abstract: | Gene targeting was used to delete exon 2 of mouse DOR-1, which encodes the δ opioid receptor. Essentially all 3H-[D-Pen2,D-Pen5]enkephalin (3H- DPDPE) and 3H-[D-Ala2,D-Glu4]deltorphin (3H-deltorphin-2) binding is absent from mutant mice, demonstrating that DOR-1 encodes both δ1 and δ2 receptor subtypes. Homozygous mutant mice display markedly reduced spinal δ analgesia, but peptide δ agonists retain supraspinal analgesic potency that is only partially antagonized by naltrindole. Retained DPDPE analgesia is also demonstrated upon formalin testing, while the nonpeptide agonist BW373U69 exhibits enhanced activity in DOR-1 mutant mice. Together, these findings suggest the existence of a second delta-like analgesic system. Finally, DOR-1 mutant mice do not develop analgesic tolerance to morphine, genetically demonstrating a central role for DOR-1 in this process. |
| Keywords: | controlled study; gene deletion; exons; nonhuman; mouse; animals; mice; mice, knockout; animal tissue; gene targeting; animal experiment; neuromodulation; drug receptor binding; immunocytochemistry; spinal cord; morphine; analgesics, opioid; oligopeptides; analgesia; drug tolerance; knockout mouse; morphine tolerance; injections, spinal; enkephalin[2,5 dextro penicillamine]; naltrindole; analgesic activity; tritium; delta opiate receptor; deltorphin; injections, intraventricular; receptors, opioid, delta; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; intracerebroventricular drug administration; priority journal; article; enkephalin, d-penicillamine (2,5)-; 4 [alpha (4 allyl 2,5 dimethyl 1 piperazinyl) 3 hydroxybenzyl] n,n diethylbenzamide; leucine enkephalin[2 dextro alanine 6 cysteine]; n methyl n [7 (1 pyrrolidinyl) 1 oxaspiro[4.5]dec 8 yl]benzeneacetamide |
| Journal Title: | Neuron |
| Volume: | 24 |
| Issue: | 1 |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Date Published: | 1999-09-01 |
| Start Page: | 243 |
| End Page: | 252 |
| Language: | English |
| DOI: | 10.1016/s0896-6273(00)80836-3 |
| PUBMED: | 10677041 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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